This invention relates to a process for the preparation of activated pharmaceutical compositions which have a high degree of bioavailability because of their good absorbability in the digestive tract. The field of art to which this invention pertains belongs to class 424 of the U.S. patent classification.
One prior art process for the preparation of a pharmaceutical composition is disclosed in Japanese Patent Publication No. 5798/1960. This process comprises adding Carbowax to chloroamphenicol palmitate, dissolving this mixture in a hot hydrophilic organic solvent, and then cooling the resulting solution rapidly to obtain a finely divided amorphous form of chloramphenicol palmitate. However, the composition prepared by this process has poor redispersibility in water because it contains Carbowax having a low melting point.
Another prior art process for the preparation of a pharmaceutical composition is disclosed in Japanese Patent Layed Open No. 2316/1979. This process comprises providing a blend of nifedipine, a first additive selected from glycerol, vegetable oils, and the like, and a second additive selected from polyvinyl pyrrolidone, methyl cellulose, hydroxypropyl cellulose, and the like; dissolving this blend in an organic solvent; and then removing the organic solvent from the resulting solution. However, this process has the disadvantage that the use of large amounts of organic solvent involves a great risk.
An organic solvent is used as the solvent in both of the above-described processes. In this respect, they are distinguished from the process of the present invention in which water is used as the dispersion medium.
In addition, an art analogous to the present invention is found in Japanese Patent Publication No. 42390/1971. Specifically, there is disclosed a process for the preparation of a suspension of chloramphenicol palmitate that is scarcely soluble in water, which comprises melting a mixture of chloramphenicol palmitate and a surface-active agent and then grinding this melt in an aqueous solution of a water-soluble high-molecular substance (e.g., methyl cellulose) by means of a colloid mill. However, the chloramphenicol palmitate included in the melt may be closely combined with the surface-active agent and be different from chloramphenicol palmitate itself. Moreover, this analogous art is directed to the preparation of suspensions. Thus, the novelty of the present invention is not denied by this analogous art.
Another art analogous to the present invention is found in Japanese Patent Publication No. 33676/1970. This relates to a process for the preparation of a finely divided suspention of an organic acid ester of chloramphenicol that is scarcely soluble in water, which comprises melting a mixture of the organic acid ester of chloramphenicol and a surface-active agent, dispersing this melt in warm water, and then cooling the resulting aqueous dispersion to precipitate the organic acid ester of chloramphenicol in the presence of, for example, polyvinyl alcohol. Again, a mixed melt of an organic acid ester of chloramphenicol and a surface-active agent is used in this process. However, the organic acid ester of chloramphenicol included therein may be closely combined with the surface-active agent to form a substance different from the organic acid ester of chloramphenicol itself. Moreover, it is certain that the formation of micelles of the surface-active agent occurs in the suspension prepared by this process, as contrasted with the process of the present invention in which no micelle formation is recognized. Furthermore, this analogous art is also directed merely to the preparation of suspensions. Thus, the novelty of the present invention is not denied by this analogous art, either.